Tumefactive Demyelinating Lesion Induced by Infliximab in a Patient with Rheumatoid Arthritis: A Case Report Study

A RARE CASE OF CONJUNCTIVAL AND SCLERAL NECROSIS FOLLOWING ANTERIOR SUB-TENON TRIAMCINOLONE ACETONIDE INJECTION IN A PEDIATRIC PATIENT

Artificial intelligence is not an autonomous existential threat. Intelligence-the ability to solve problems-is distinct from agency, the ability to set and pursue goals. AI systems exhiabit superhuman intelligence but remain entirely devoid of intrinsic agency. The true existential risk does not come from AI itself, but from humans wielding AI to manipulate perception at unprecedented scale. AI's extraordinary capacity to distort reality enables mass behavioral modification, culminating in an inevitable epistemic collapse. As synthetic content proliferates exponentially, the ratio of authentic to synthetic information trends toward zero. Centralized verification systems cannot contain this flood. The only viable defense is decentralized collective verification, as demonstrated by Wikipedia, X's Community Notes, Reddit's moderation, Stack Overflow's peer-review, and the scientific method itself. Humanity's collective intelligence, acting as a distributed neural network, is the only force capable of distinguishing reality from illusion. The existential threat posed by AI is human-driven. Its solution must be as well.

From Repeated Misdiagnosis to Confirmed Diagnosis – A Complete Record of the Treatment of a Retroperitoneal Abscess Caused by Appendiceal AdenocarcinomaYouheng Wang1,2,3,4#, Jian Li1,2,3,4#, Shu Tang5, Tianran Chen1,2,3,4, Chunguang Li1,2,3,4, Qun Qian1,2,3,4*, Daojiang Li1,2,3,4*1.Department of Colorectal and Anal Surgery of Zhongnan Hospital of Wuhan University2.Wuhan Clinical Research Center for Constipation and Pelvic Floor Disorders3.Hubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University)4.Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei Province5.Surgery Department of Zhongnan Hospital of Wuhan University#Contributed equally.*Correspondence toDaojiang Li, daojiangli@whu.edu.cn, Qun Qian, qunqian2007@163.comAddress: No. 169, Donghu Road, Wuchang District, Wuhan, Hubei province, ChinaThe email of other authorsYouheng Wang, wangyouheng@whu.edu.cn Jian Li, 2022283030091@whu.edu.cn. Shu Tang, tangshu3328415@qq.com Tianran Chen, Chentianr1996@163.com Li Chunguang, leecg1970@163.com.Abstract: Retroperitoneal abscess secondary to appendiceal or colonic tumors is clinically rare and prone to misdiagnosis. This article reports the case of a 65-year-old male patient who experienced recurrent right upper abdominal pain and sought treatment at multiple hospitals. He was successively diagnosed with pyelonephritis, aortic ulcer, and periappendiceal abscess, and received treatments including anti-infective therapy and vascular intervention. Initial CT and PET-CT scans only indicated ascending colon diverticulum and inflammatory exudation, with no tumor signs observed during colonoscopy. Six months later, his symptoms worsened, and necrotic tissue was obtained through ultrasound-guided puncture, pathologically confirming appendiceal adenocarcinoma (MSS type, with KRAS p.G12V and APC p.S1344* mutations). The drainage fluid CEA level exceeded 1500 ng/mL, and imaging suggested liver metastasis. After evaluation by a multidisciplinary team (MDT), the patient underwent neoadjuvant chemotherapy with the XELOX regimen. Due to unresolved symptoms and poor tolerance, a right hemicolectomy combined with en bloc resection of the retroperitoneal mass and radiofrequency ablation of liver metastases was ultimately performed, with good postoperative recovery. This case highlights three key clinical points: (1) In elderly patients with retroperitoneal abscess in the right colon region, the possibility of tumors should be highly suspected. CT/ultrasound-guided puncture biopsy combined with tumor marker analysis (CEA, CA199) and cytological examination of drainage fluid is recommended as a first-line diagnostic strategy. (2) Inflammatory reactions can obscure tumor imaging features, and even PET-CT has limitations. Dynamic monitoring and pathological verification are essential. (3) For cases with poor drainage (predominantly necrotic tissue) or ineffective conservative treatment, direct surgery can be a preferred option. However, precise evaluation of tumor invasion extent by an MDT is crucial to avoid damage to critical structures such as the duodenum and ureter.Keywords: Appendiceal tumor, Periappendiceal abscess, Retroperitoneal abscess, Puncture biopsy

Title PageTitle: Letter to the editor : Family strategies for managing childhood cancer: Using traditional and complementary medicine in Southern EgyptArticle type: Letter to the EditorCorrespondence: 1. Syeda Ailia KazmiEmail: ailia.kazmiii@gmail.comInstitute: Jinnah Sindh Medical UniversityAddress: Karachi, PakistanORCID: 0009-0009-5762-8505Word count: 493Conflict of interest: noneDeclaration: noneAcknowledgments: noneFunding: noneAI Declaration: In order to facilitate comprehension, this manuscript employs artificial intelligence (AI) tools to paraphrase and better the clarity of its content. The authors are responsible for all substantive information, data, and original ideas presented in this manuscript, despite the use of AI-assisted tools to rephrase specific sections. The integrity of the scientific content has been meticulously maintained through human oversight and validation, and no portion of this manuscript is wholly generated by AI.

Background and aims: To assess clinical outcomes and quality of life (QoL) of children, adolescents, and young adults (C-AYAs) with chordomas (CH) or chondrosarcomas (CS) after pencil beam scanning proton therapy (pbsPT). Methods: Seventy-six C-AYAs treated between 1999-2023 were included. Median age was 16.6 years (1.5-25.4). Forty-four (57.9%) were AYAs (15-25 years). Most tumors were CHs (n=49; 64.5%) and located in the skull-base (68.4%). Median radiation dose was 73.8 Gy (RBE) (54-75.6). Twenty-six (34.2%) patients underwent complete resection. PEDQOL questionnaire was used to assess QoL. Kaplan–Meier and log-rank test were used for the analysis. Results: With a median follow-up of 88.4 months (range, 1.8 – 257.6), 9 (11.8%) patients died. Local failure only developed in 9 (11.8%) patients. Two (2.6%) presented with distant failure only and another (1.3%) had both. Seven-years overall survival (OS), local control (LC), and distant control (DC) were 86.3%, 87.7% and 95.7%, respectively. Children when compared to AYAs had worse 7-years DC (90% vs. 100%, p=0.049). Surgical resection vs. biopsy was associated with better 7-years LC (87.1% vs. 67.7%, p=0.031). Recurrent tumors showed worse OS, LC, and DC (94.5% vs. 44.6%, p<0.001; 93.2% vs. 36.6%, p<0.001; 98.3% vs 77.6%, p=0.003). Seven-years freedom from grade ≥3 late toxicity was 83.1%. Three (3.9%) children with CH developed secondary tumors. QoL did not differ from a healthy cohort 2 years after pbsPT. Conclusions: Excellent clinical outcomes with acceptable long-term toxicity and QoL were observed for C-AYAs with CH/CS after pbsPT. Recurrent tumors, children, and lack of surgical resection was associated with worse prognosis.

Purpose : Women of childbearing age may receive HPV vaccination during pregnancy, yet evidence on birth defects (BDs) risks remains limited. This study evaluates associations between peri-conception HPV vaccination and BDs. Methods: This population-based retrospective cohort study included pregnancies conceived between March 2018 and December 2021 in Xiamen, China. Propensity score matching based Poisson regression was used to estimate the adjusted relative risk (aRR) of exposure for total BDs and 10 organ system-specific BDs. Two subgroup analyses, including different exposure windows and vaccine valences, six sensitivity analyses, and a negative control analysis were performed. Results: A total of 177,574 pregnancies were included, of which 566 were exposed to the HPV vaccine during the Peri-conception period. The rate of Peri-conception vaccine exposure increased from 0.10% in 2018 to 0.58% in 2021. After 1:4 PSM, peri-conception HPV vaccination was not associated with an increased risk of total BDs (aRR 0.77, 95% confidence interval [CI] 0.42-1.42). Similarly, no significant association was found between HPV vaccination and the risk of 10 organ system-specific BDs. In subgroup analyses, exposure during pre-30 days (aRR 0.59, 95%CI 0.23-1.48) and the first trimester (aRR 0.61, 95%CI 0.14-2.69), exposure to the 4vHPV (aRR 1.25, 95%CI 0.62-2.51) and 9vHPV (aRR 0.57, 95%CI 0.13-2.49) vaccines were not associated with a higher risk of total BDs. All sensitivity and negative control analyses demonstrated the robustness of the results. Conclusions: Our evidence suggests that exposure to the HPV vaccine before and during early pregnancy does not increase the risk of birth defects. This conclusion helps increase the willingness of women of childbearing age to receive HPV vaccination. Trial registration: This study was registered at ClinicalTrials.gov (NCT06180447).

DEFINING NORMAL REFERENCE RANGES OF LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN AMONG DIFFERENT VENDORS: ARE WE THERE YET?Nanna Michele1 MD, Romero Acero Laura Marcela1 MD, Lee Pei-Lun 2 MDCardiac Care & Vascular Medicine / Albert Einstein College of MedicineJacobi Medical Center, Department of Medicine/Albert Einstein College of MedicineStrain and strain rate imaging have evolved significantly since their introduction two decades ago, providing an objective means to quantify both regional and global myocardial function [1]. Initially developed using tissue Doppler strain, strain imaging has largely transitioned to speckle-tracking echocardiography (STE), a technique that is angle-independent and offers improved feasibility and reproducibility. Left ventricular global longitudinal strain (LVGLS) has become an established measure of left ventricular (LV) systolic function with numerous clinical applications. However, despite its promise, LVGLS has not yet been widely adopted in real-world clinical practice. One major barrier is the variability across different echocardiographic vendors, which introduces inconsistency in measurements and complicates standardization efforts.Traditionally, left ventricular ejection fraction (LVEF) has been the most commonly used parameter for assessing LV systolic function and predicting outcomes. However, despite its widespread use, LVEF has notable limitations, including significant intra- and inter-observer variability, dependence on geometric assumptions, and susceptibility to technical artifacts such as endocardial dropout and foreshortening of the apex. Similar challenges exist for LVGLS, where accurate endocardial contour delineation and motion tracking are crucial for reliable assessment. Reproducibility of LVGLS using different vendors’ algorithm software remains controversial and has been described as acceptable by some [2] or shown to have significant discrepancies by others [3-5].Advancements in speckle-tracking echocardiography, including machine learning-driven algorithms, have improved strain analysis. However, a key limitation of strain imaging is that measurements remain dependent on proprietary software algorithms, leading to variability between vendors. Moreover, despite abundant literature, defining universal reference ranges remains a challenge, as different software platforms yield slightly different results. A proposed solution has been the use of intra-institutional vendor independent software capable of obtaining off line strain measurements. These vendor independent strain software packages have evolved but have not undergone rigorous external validation studies.The study by Arockiam et al. [6] addresses this gap by evaluating normal reference ranges for LVGLS using contemporary, vendor-neutral strain software in a cohort of healthy individuals. The authors examined 100 subjects across different age groups, using echocardiographic scans from General Electric (GE) and Philips systems. Four strain software packages—TomTec, EchoPAC, VVI, and Epsilon—were used to quantify LVGLS, enabling direct comparative and regression analyses. Their findings indicate that mean LVGLS values varied slightly across the four software packages, with EchoPAC producing the most negative strain values and VVI yielding the least negative values. Regression analyses identified sex, heart rate, LVEF, and the choice of strain software (particularly EchoPAC and VVI vs. TomTec) as significant contributors to LVGLS measurement variability. Despite differences across the four software platforms, the study provides reference ranges that may aid in defining normal, abnormal, and borderline LVGLS values for clinical application.Based on these results, the authors conclude that LVGLS measurements were feasible across all four strain software on both GE and Philips scans in this study. While acknowledging differences among the four strain software packages, by reporting LLNs and their 95%CI the authors provide helpful reference ranges to define normal, abnormal and borderline LVGLS values to enable clinical application. The results led the authors to cautiously recommend using the same strain software and their own respective reference ranges for interpreting and comparing LVGLS measurements.Importantly, the authors demonstrate that the inter-vendor variability of LVGLS is now comparable to, or even smaller than, the variability seen with LVEF. This marks a significant step toward the routine clinical application of LVGLS as an alternative or adjunct to LVEF. An increasing number of studies have suggested that GLS is superior to EF as a measure of LV function and as a predictor of mortality and cardiac events [7-10] . Previous reports have suggested that an absolute GLS of -12% represents severe systolic dysfunction and carries an adverse prognosis, and -15–16% identifies patients with relatively preserved EF at higher risk for future events. However, LVGLS reference range values associated with risk tiers have yet to be firmly established, in part due to lack of established lower limit of normal values.While the study represents a significant contribution to the field, some limitations should be acknowledged. The cohort predominantly comprised younger subjects, which may not reflect the typical age distribution seen in clinical practice. Since older patients often have more comorbidities affecting myocardial mechanics, the findings may not be fully generalizable. Most participants were white, limiting the applicability of the findings to ethnically diverse populations. A number of studies have provided reference ranges for specific ethnic groups. In the 2012 JUSTICE (Japanese Ultrasound Speckle Tracking of the Left Ventricle) study [5] of 817 healthy mostly male volunteers with average age 36 years, the overall mean full thickness, peak systolic GLS using GE equipment was reported as -21.3+ 2.1% . In a 2014 Italian study [11] of 260 Caucasian healthy mostly female volunteers with average age 44 years, the mean full-thickness, peak systolic GLS using GE equipment was reported as -21.5 +2.0% (lower limits of normal or average: 2 SD was 16.9% for men and 18.5% for women). Different values were obtained in a 2009 multicenter (Australian, European and American) study [12] of 242 healthy mostly female volunteers with average age 51 years in which mean full-thickness, peak systolic GLS using GE equipment was reported as -18.6+ 0.1%, with no significant differences among geographical regions. Given known ethnic differences in cardiac structure and function, further studies incorporating broader demographic diversity are needed.The study does not provide data on whether LVGLS measurements obtained from different ultrasound machines (GE vs. Philips) in the same patient yield consistent results across all vendor-neutral software platforms. This remains a crucial question for laboratories that use multiple echocardiographic systems. Additionally, the study focused solely on LVGLS and did not assess global circumferential strain, global radial strain, or strain rate measurements. These parameters are less commonly used in clinical practice due to their greater variability, but further investigations into their standardization remain necessary.Similarly, GLS is highest in the endocardium and lowest in the epicardium. To assess inter-vendor global strain differences the study results only apply to endocardial GLS, the only parameter that could be provided by all vendors. Results may not be valid if region of interest for GLS is set in the midwall, epicardial, or full thickness. Indeed, most companies now include software capable of mid/full wall tracking which preliminary data have shown to have similarly good inter-vendor bias and reproducibility as endocardial GLS [13].There is currently lack of reference values for segmental strain measurements in part due to suboptimal reproducibility and large inter-vendor measurement variability. The current study does not provide information regarding quantitative assessment of the magnitude of regional deformation. This leaves open the possibility that, inter-vendor differences for segmental strain values may be considerably higher than that reported for global values. The extent of spatial smoothing aimed at reducing noise in the regional tracking of speckles may vary in the different algorithms used by each vendor and may contribute to inter-vendor variability. This gap in knowledge relegates regional strain measurements to assessment of regional differences in polar strain maps rather than precise definition of numerical segment-specific strain values. While reductions in local strain may correctly identify areas of inflammation or fibrosis, the availability of reference values might enhance the ability to quantify regional abnormalities as compared to other imaging techniques.Thanks to continued collaboration between vendors and potential sharing of proprietary software has resulted in further reduction in inter-vendor variability. A recent report of the European Association of Cardiovascular Imaging (EACVI) Strain Standardization Task Force [13] aimed at comparing the current inter-vendor variability and reproducibility to the findings from their previous 2013 results evaluated 372 echocardiographic examinations performed in sixty-two subjects with a wide range of left ventricular (LV) function (ejection fraction from 30% to 64%) using ultrasound systems from six manufacturers.The results showed that both endocardial and mid/full-wall GLS measurements were comparable and within a very narrow range (maximum inter-vendor bias of 0.9% strain units) whereas in 2013, the maximum absolute difference was 3.7 % strain units, leading the authors to conclude that in contrast to the situation ten years earlier, a substantial improvement in inter-vendor bias has been accomplished. In addition, most companies now allow mid/full-wall tracking, which had similarly good inter-vendor bias and reproducibility as endocardial GLS.The study by Arockiam et al. [6] represents an important step toward the standardization of LVGLS measurements across different software platforms. By providing vendor-neutral reference ranges, the authors offer valuable insights that may facilitate the integration of strain imaging into routine clinical practice. However, persistent variability among independent vendors, albeit reduced, underscores the need for continued refinement in strain software and external validation in larger, more diverse populations. Moving forward, widespread adoption of vendor-neutral strain software, along with further multicenter studies, will be crucial for achieving true standardization. In the interim, clinicians should remain aware of the potential measurement discrepancies among software packages and ensure consistency by using the same strain analysis tool for serial patient evaluations.REFERENCES[1]. Sutherland GR, Di Salvo G, Claus P, et al. Strain and strain rate imaging: a new clinical approach to quantifying regional myocardial function. J Am Soc Echocardiogr. 2004;17(7):788-802.[2]. Manovel A, Dawson D, Smith B, et al. Assessment of left ventricular function by different speckle-tracking software. Eur J Echocardiogr. 2010;11(5):417-21.[3]. Biaggi P, Carasso S, Garceau P, et al. Comparison of two different speckle tracking software systems: does the method matter? Echocardiography. 2011;28(5):539-47.[4]. Nelson MR, Hurst RT, Raslan SF,et al. Echocardiographic measures of myocardial deformation by speckle-tracking technologies: the need for standardization? J Am Soc Echocardiogr. 2012;25(11):1189-94.[5]. Takigiku K, Takeuchi M, Izumi C, et al. Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle (JUSTICE) study. Circ J. 2012;76(11):2623-32.[6]. Arockiam A D, Dong T, Agrawal A, et al. Reference ranges of left ventricular global longitudinal strain by contemporary vendor-neutral echocardiography software in healthy subjects. Echocardiography (in press).[7]. Ersbøll M, Valeur N, Mogensen UM, et al. Prediction of all-cause mortality and heart failure admissions from global left ventricular longitudinal strain in patients with acute myocardial infarction and preserved left ventricular ejection fraction. J Am Coll Cardiol. 2013;61(23):2365-73.[8]. Mignot A, Donal E, Zaroui A , et al. Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study. J Am Soc Echocardiogr. 2010;23(10):1019-24.[9]. Stanton T, Leano R, Marwick TH. Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring. Circ Cardiovasc Imaging. 2009;2(5):356-64.[10]. Haugaa KH, Grenne BL, Eek CH, et al. Strain echocardiography improves risk prediction of ventricular arrhythmias after myocardial infarction. JACC Cardiovasc Imaging. 2013;6(8):841-50.[11]. Kocabay G, Muraru D, Peluso D, et al. Normal left ventricular mechanics by two-dimensional speckle-tracking echocardiography. Reference values in healthy adults. Rev Esp Cardiol (Engl Ed). 2014;67(8):651-8.[12]. Marwick TH, Leano RL, Brown J, et al. Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging. 2009;2(1):80-4.[13]. Balinisteanu A E, Duchenne J, Puvrez A,et al. Inter-vendor variability in two-dimensional speckle tracking strain: a ten-year follow-up on the strain standardization task force inter-vendor comparison study. Eur. Heart J. Cardiovasc. Imaging. 2025; 26, Issue Supplement_1.

Functional trait similarity in metacommunities, important for community assembly and ecological resilience in the face of environmental changes on landscapes, is structured by niche and stochastic processes. Yet, uncertainties about the importance of these processes remain because opposing responses of different species to environmental variables can obscure the detection of niche patterns related to environmental variation. To counter this, we propose examining metacommunity assembly patterns detected within clusters of species that share similar functional traits. We focused on groups of crustacean zooplankton species in boreal lake metacommunities that are similar in body size, feeding guild, and phylogenetic distance. The crustacean zooplankton species composition of lake metacommunities in three regions of Quebec, Canada (Saguenay, Côte-Nord and Schefferville) were surveyed using organismal bulk sample cytochrome oxidase I (COI) metabarcoding. Species were clustered according to their similarity using the three traits, and redundancy analysis and variation partitioning were applied to parse the relative influences of niche processes (environmental variables) and stochastic processes (spatial vectors) in the structuring of the communities within-cluster, between-clusters, and unclustered. We found that stochastic processes were the main source of influence in all three regions, but especially in Schefferville, the northernmost region. Cladocerans were more strongly influenced by niche processes than copepods. Finally, we found that analyzing the community assembly processes for all zooplankton species together offered less explanatory power and missed environmental variables that were key in the structuring of the different groups of ecologically similar species.

Background: Ischemic stroke (IS) is a serious cerebrovascular disease. Excessive levels of acetylated proteins are related to neuronal resistance to ischemia. Therefore, it is crucial to screen for histone acetylation regulatory-related biomarkers for IS. Methods: To identify differentially expressed genes (DEGs) in GSE16561, we executed a differential expression analysis (normal versus IS). Meanwhile, key module genes connected with single-sample gene set enrichment analysis (ssGSEA) enrichment score of histone acetylation regulatory related genes (HARGs) were identified by weighted correlation network analysis (WGCNA). Then, histone acetylation regulatory-related DEGs (HAR-DEGs) were attained by overlapping DEGs and key module genes. Three machine learning algorithms, expression and receiver operating characteristic (ROC) analysis, were employed to screen histone acetylation for regulatory related biomarkers. Afterwards, we carried out functional enrichment and immune microenvironment analysis on biomarkers.The disease association of biomarkers was analyzed. Finally, expression levels of biomarkers were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results:A total of 550 DEGs and 137 key module genes related to ssGSEA enrichment scores of HARGs were added up respectively. Through intersection of DEGs and key module genes, 44 HAR-DEGs were selected. Moreover, CREBBP and CKAP4 were identified as histone acetylation regulatory-related biomarkers in IS. We found that both biomarkers were linked with some immune-related signaling pathways, such as complement and coagulation cascade pathways. In addition, CREBBP was inversely linked with score of CD8 + T cells, while CKAP4 was positively correla t ed with score of M0 macrophages. Both biomarkers were found to be associated with brain injury and disease. Finally, in line with the outcomes of transcriptome data analysis, expression of CREBBP and CKAP4 was significantly elevated in clinical IS sample compared to versus control samples. Conclusion:In summary, we obtained two biomarkers ( CREBBP and CKAP4) that are connected with regulation of histone acetylation in relation to IS. These findings may laya theoretical basis for treatment of IS.

Background: Graves’ disease (GD), which is prevalent among endocrine system disorders, significantly impacts patients’ health. This study, aiming to uncover the underlying mechanisms, uses the summary - data - based Mendelian randomization analysis (SMR) to explore the causal relationship between genes and GD using a multi - omics method. The purpose of this study is to provide a new perspective for further understanding the complex biological mechanism of GD and accurately identifying potential drug targets, thereby potentially leading to more effective treatments. Methods: Causal links between GD and genetic markers (mQTL, eQTL, pQTL) were assessed. Colocalization analysis and SMR for methylation-gene expression and gene expression-protein were done. DsigDB predicted drugs. Results: 1,772 DNAm sites related to genes at mQTL, eQTL levels and identified proteins. AGER and AIF1 were common. AIF1 was a consistent high-risk factor (mQTL: OR 1.09, 95% CI 1.04-1.15; eQTL: OR 1.44, 95% CI 1.21-1.71; deCODE-pQTL: OR 3.17, 95% CI 2.07-4.84; UKB-PPP-pQTL: OR 3.46, 95% CI 2.18-5.49). AGER had a positive DNA methylation-gene expression correlation, AIF1 negative, both with co-localization. AGER’s gene expression-protein was negative, AIF1’s positive. Drugs OLEANOLIC ACID, RUTIN, Estriol, GW9662 for AGER and QUINOLINE for AIF1 were predicted. Conclusion: The study reveals new insights into GD, proposes AGER and AIF1 as targets, aiding GD treatment, but needs experimental validation.

A dual-pathway approach combining anticoagulation and antiplatelet (APT) therapy is challenging for the trade-off of benefits and bleeding risks. By selectively inhibiting the coagulation cascade-factor Xa or thrombin, novel oral anticoagulants (NOACs) combined with APT may be more conducive to achieve this balance. The study aimed to evaluate comprehensively the role of NOACs combined with APT in acute coronary syndrome (ACS) and AF undergoing PCI or complicating ACS. To identify relevant RCTs, a systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. We summarized the results using the Mantel–Haenszel (M-H) random-effect models. The risk ratio (RR) value and 95% confidence intervals (CI) calculated were applied to dichotomous outcomes. Seventeen trials randomizing 49345 participants reported our predefined outcomes. For ACS patients, compared with control groups, NOACs combined with APT significantly reduced MACEs , ST, ischemic stroke and all-cause death , accompanied by increased TIMI major bleeding , trial-defined primary bleeding and ISTH major bleeding . For patients with AF undergoing PCI or complicating ACS, NOACs plus APT markedly decrease the risk of bleeding compared with the control groups, including TIMI major bleeding , trial-defined primary bleeding , ISTH major bleeding and ISTH CRNM bleeding. However, there were no obvious differences in all efficacy outcomes. These findings support the application of NOACs combined with APT in patients with ACS and AF undergoing PCI or complicating ACS; however, appropriate regimens should be designed to obtain the maximal benefit and balance the bleeding risk in clinical practice.

Background and Purpose: Chronic stress affects brain functions leading to the development of mental disorders like anxiety and depression, as well as cognitive decline and social dysfunction. Among many biological changes in chronically stressed brains, disruptions in AMPA Receptor (AMPAR)-mediated synaptic transmission in the hippocampus are associated with stress responses. We have revealed that low-dose ketamine rapidly induces the expression of GluA1-containing, GluA2-lacking Ca2+-Permeable AMPARs (CP-AMPARs), which enhances glutamatergic synaptic strength in hippocampal neurons. Additionally, subanesthetic low-dose ketamine decreases anxiety- and depression-like behaviors in naïve animals. In addition to reducing depression, some research indicates that ketamine may have protective effects against chronic stress in both humans and animals. However, the role of CP-AMPARs in the actions of ketamine’s antistress effects is largely unknown. Experimental Approach: We use whole-cell patch-clamp recordings from CA1 pyramidal neurons in female and male hippocampal slices and multiple behavioral assays including reciprocal social interaction, contextual fear conditioning, and tail suspension test. Key Results: We demonstrate that low-dose ketamine treatment reverses chronic restraint stress (CRS)-induced social dysfunction, hippocampus-dependent fear memory loss, and depression-like behavior in both female and male mice. Furthermore, we show that the ketamine-induced antistress effects on these behaviors are dependent on CP-AMPAR expression. Conclusion and Implications: Our findings suggest that subanesthetic low-dose ketamine rapidly triggers the expression of CP-AMPARs in the hippocampus, which induces antidepressant and antistress effects.

The evolution of phenotype has historically been studied by classifying traits into categories, as traits within each category often exhibit close associations. However, these categories are not independent of one another. Thus, the phenotype may function as an integrated set of traits rather than as isolated units. In this study, we employed various phylogenetic comparative methods to explore evolutionary correlations among traits, estimate and compare phylogenetic signals, and evaluate evolutionary models to assess the validity of the historical categorization of phenotypic traits in spiny lizards of the genus Sceloporus. We categorized these traits as either morphological or life-history traits, including eight morphological traits and seven life-history traits, such as trunk length, head width, snout-vent length, clutch size, hatchling length, and size at maturity. Our analyses revealed covariation in the evolution of traits both within and across categories. Differences in phylogenetic signals between categories were also observed, though these results should be interpreted with caution. Additionally, the evolutionary models varied between categories. Our findings suggest that estimates of phylogenetic signals and covariation between morphological and life-history traits are independent of historically assigned categories. Therefore, this supports the notion that traits should be compared and analyzed in an integrated manner, regardless of their category. We discuss how evolutionary mechanisms, such as fecundity selection, may influence traits across different categories (e.g., trunk length, hatchling length, and clutch size), challenging the appropriateness of traditional phenotypic categorization in evolutionary studies of Sceloporus.

As global temperature rises, fish are predicted to become smaller. Body size is a fundamental trait impacting many aspects of an animal’s life history and ecology, and understanding how it may respond to climate change in particular fish groups, especially commercial or keystone species, is critical. The slimeheads (Family Trachichthyidae) include several commercially important species, but because they are deep-dwelling, long-lived fish, which reproduce slowly, directly testing the temperature-size relationship in this family is challenging. Fortunately, the Trachichthyidae have a long evolutionary history beginning in the Cretaceous and their fossil record provides empirical data on the response of this family to past climate change events. In this study, we leveraged the extensive fossil record of the Late Cretaceous trachichthyid genus Hoplopteryx from the British Chalk Group of southern England, United Kingdom to test whether its size declined at higher temperatures. Standard Lengths were measured from complete individuals and estimated from partial remains. Seawater palaeotemperature estimates were derived from oxygen stable isotope values (δ18O) of the bulk chalk rock surrounding the fossils using standard techniques and assumptions. Individual fish ranged from 56.3 to 253.5 mm in length, and measured seawater temperature estimates ranged from 19.5 to 27.1 °C. We recorded a significant negative correlation between estimated seawater temperature and Standard Length in the most common species Hoplopteryx lewesiensis, supporting the prediction that higher temperatures lead to smaller body size. In addition, we found a significant negative correlation between the lengths of H. lewesiensis and carbon stable isotope values (δ13C) of the chalk matrix, suggesting that other environmental factors such as primary productivity and/or the burial of organic matter may also have affected body size.

Previous phylogeographic studies based on mitochondrial DNA (mtDNA) markers have revealed a complex evolutionary history for the Italian wall lizard, Podarcis siculus, characterized by a geographically structured diversity of lineages. These lineages were shaped by allopatric divergence within multiple southern refugia, likely during the Pleistocene. In this study, a total of 294 Podarcis siculus specimens from 121 localities were genetically analyzed using microsatellite markers to: (i) assess whether the genetic substructure detected in mtDNA is reflected in nuclear microsatellite markers, (ii) evaluate potential cases of mito-nuclear discordance, and (iii) determine the extent of admixture resulting from gene flow between mtDNA haplogroups. The analysis identified eight genetic clusters, whose spatial distribution partially aligns with the mitochondrial structure. However, several discrepancies were observed, primarily in Southern Italy and Sicily. These include differences in the location of the contact zone between the two main lineages and the absence of genetic structure in some regions (e.g., Sicily), despite the presence of multiple parapatric mtDNA lineages. Possible explanations for mito-nuclear discordance involve a combination of factors, including the different evolutionary timescales captured by mitochondrial DNA and microsatellites, differential introgression of nuclear versus mitochondrial genes, and distinct dispersal patterns, potentially influenced by sex-biased philopatry, which affect gene flow among populations.

Epifaunal bivalves include reef building organisms that provide several important ecological functions in coastal marine environments. Evaluating the distributional patterns and population sizes is key in assessing the total and relative contribution of species towards these functions and can aid in improving spatial planning and management. In this paper, the utility of combining distribution models and models of abundance to improve population size estimates of epifaunal bivalves on the Swedish west coast was investigated. Models were fitted to predict occurrences and densities of three, both native and invasive, ecologically important bivalve species (blue mussel, Mytilus edulis; Pacific oyster, Magallana gigas and European oysters, Ostrea edulis). Bootstrapping methods were used to estimate model performance and error margins around the final predictions. Results from the distribution models show considerable overlap in use of shallow habitat by the native blue mussels and the invasive Pacific oyster, while the European oyster resided mostly in deeper habitats. There were however differences in larger geographical distribution patterns in all species. The use of distribution and abundance models drastically altered population estimates in species where models performed well, compared to methods without the use of models or only distribution models. Importantly, estimates of total abundance when translated to biomass estimates indicated that the invasive Pacific oyster likely contributes the most to ecosystem functions associated with epibenthic bivalves in this area.

Objective: To describe and classify mistreatment during maternity care as described by a diverse set of women across the United States. Design: Interpretive Description Qualitative Analysis Setting: Qualitative data were collected via a web-based survey (n=1151) and in semi-structured interviews (n=25). Sample: Adult women with a history of cesarean who had a subsequent birth (of any mode) in the United States in the 5 years preceding study participation. Methods: Deductive Content Analysis was employed using a priori codes based on Bohren et al.’s Typology of Mistreatment of Women during Childbirth framework. Results: Participants described all eight types of mistreatment. Participants with marginalized identities and socioeconomic disadvantage were more likely to describe mistreatment. Consequences of mistreatment in maternity care described by participants included healthcare system distrust, reduced postpartum healthcare utilization, and maternal mental health complications. Conclusions: Those most at risk for adverse maternal and infant birth outcomes were the most likely to describe mistreatment in their maternity care. In addition to inflicting birth-related trauma, this created a distrust of the healthcare system, decreased postpartum health care utilization, and resulted in missed opportunities for postpartum screening and follow-up for those at greatest risk of maternal mortality, severe morbidity, and postpartum mental health complications.

Objective: Resource constraints limit the use of evidence-based clinical guidelines (CPGs). This study describes the adaptation and scale-up of a context-specific maternity care pocket guide, initially co-created in Zanzibar, to five urban health facilities in Dar es Salaam, Tanzania. Design: Participatory, iterative co-creation. Settings: Five government health facilities in Dar es Salaam (2021). Population: Maternity care providers, researchers, women and other stakeholders. Methods: A structured, flexible CPG adaptation model was applied, combining a mixed-methods situational analysis, review of global and national CPGs, and iterative feedback via focus groups and individual reviews until saturation. The guide was then pilot-tested and implemented. Main Outcome Measures: Co-creation process, PartoMa Pocket Guide and implementation strategy. Results: Two review cycles with 54 frontline providers, two external reviews (11 international experts and 10 Dar es Salaam Health Management Team members), and two consultation meetings with a 28-member core team. The process produced a 24-page infographic pocket guide of CPGs, covering routine care and common complications during childbirth, and a dissemination strategy including in-house, low-dose, high-frequency training. Using the Zanzibar guide streamlined adaptation, revealing notable consistency across resource-constrained settings. However, the process remained time- and resource-intensive, particularly when international scientific evidence was insufficient or failed to capture urban clinical complexities. Conclusions The PartoMa CPG adaptation model effectively contextualises and scales evidence-based CPGs in high-volume, resource-constrained urban settings. Global CPG developers should integrate end-user needs from the outset for more practical and cost-effective adaptations. Funding: Danida Fellowship Centre (DFC), Ministry of Foreign Affairs of Denmark (DFC project no. 18-08-KU).

Data classification is crucial in improving medical decision-making efficiency within Medical Cyber-Physical Systems (MCPS). In this study, a hybrid data classification method is proposed for classification of heart disease data. The proposed method uses two-level data classification that integrate ensemble learning and fuzzy logic. At first level, XGBoost algorithm is used to categorize the data into two classes viz. critical and non-critical. At the second level, key clinical characteristics are extracted for each class and the severity index data are calculated. The further classified using fuzzy logic classifiers depending on the severity indices. The proposed model is tested for three different datasets to compare performance and has an accuracy of 99.50%, which is relatively higher than the algorithms compared. This hybrid methodology can improve medical decision making efficiency by providing efficient classification in real-time.

Introduction: Human movement involves a dynamic interplay of isometric, concentric, and eccentric muscle actions. There is a need to understand the contribution of the reticulospinal tract (RST) to human movement control during different muscle actions. This research aimed to determine the excitability of the RST during isometric, concentric and eccentric muscle actions. Methods: Fourteen neurologically intact participants (Age: 26 ± 7 years; Sex: 3 female, 11 male; Stature: 176 ± 8 cm; Mass: 78.5 ± 10.9 kg) performed isometric, concentric, and eccentric muscle actions with the biceps brachii. Participants performed a submaximal contraction at 25% of their isometric maximum voluntary contraction (MVC) during all muscle actions. Neurophysiological electrical stimulations to indirectly measure RST excitability consisted of conditioned (startling auditory stimulus of ≥110 dB) and unconditioned (no auditory stimulus) cervicomedullary motor evoked potentials (CMEPs). Results: Larger conditioned CMEP responses compared to unconditioned CMEPs were observed for all muscle actions (p = 0.008). However, no differences in RST excitability, inferred from the difference between conditioned and unconditioned CMEP responses, were observed across the three muscle actions (p = 0.319). Discussion: These results suggests that across isometric, concentric, and eccentric muscle actions, there are no differences in RST excitability whilst performing a submaximal contraction at 25% of their isometric MVC. It could therefore be inferred from this that RST input to motoneurons is not different between isometric, concentric, and eccentric muscle actions of the biceps brachii at relatively low contraction intensities.

Objectives: This research explores the interaction between circadian rhythms and the cellular mechanisms responsible for epileptic seizures, by integrating circadian modulation into the Epileptor-2 model. The aim is to improve understanding of the underlying dynamics and identify optimized therapeutic strategies in phase with biological circadian cycles. Methods: A circadian factor was integrated into the Epileptor-2 model to simulate daily fluctuations in neuronal excitability and seizure onset. These variations interact with pharmacological treatments, and we modeled their effects to evaluate dose adjustments and schedules aligned with circadian rhythms. The pharmacokinetics of anti-epileptic drugs were parameterized to analyze their interaction with periods of peak seizure risk. Results: Integrating circadian fluctuations in ionic dynamics into the model has provided deeper mechanistic insights into their effects on neuronal excitability and seizure onset. Our simulations indicate that adjusting drug doses and administration schedules according to patients’ biological rhythms enhances treatment efficacy and lowers seizure risk. These findings highlight the significance of personalized chronotherapy, tailored to periods of highest seizure susceptibility, for optimizing epilepsy management. Significance: This study demonstrates how circadian modulation of ion dynamics influences neuronal excitability, seizure onset, and interactions with pharmacological treatment, providing insight into the mechanisms underlying ictal discharges. By incorporating these fluctuations into the Epileptor-2 model, we offer a mechanistic understanding of circadian rhythms in epilepsy. Our approach, combining cellular with chronotherapy modeling, represents a first step toward developing a valuable tool for optimizing antiepileptic treatments based on patient’s biological rhythms, ultimately enhancing the precision and effectiveness of epilepsy management.

The South African citrus industry is facing more and more difficulties due to strict agricultural export laws and more impending, pest and disease outbreaks, and large-scale farmers’ market dominance that marginalizes small and medium-sized producers. In order to improve small citrus farmers’ competitiveness and streamline adherence to phytosanitary regulations, this study proposes the conceptual design, analysis, and evaluation of a low-cost Autonomous Mobile Robot (AMR). The AMR’s ability to autonomously traverse citrus fields, particularly underneath trees, is a crucial component that allows for the early detection of pests and diseases from unusual perspectives, and combined with human intervention for analysis reduces the design cost significantly making it potentially accessible to all farmers in South Africa. In order to develop an optimised and cost-effective AMR, the research conducted feasibility studies, iterative cost-effectiveness analyses, and a systematic identification of the needs of smallholder farmers using a holistic conceptual design methodology based on systems engineering principles utilizing GENESYS Software. By combining object avoidance, geotagging, and multi-angle imaging features, the finished design enables South African citrus farmers to effectively record and track tree health with precision agriculture. The AMR can greatly increase the sustainability and financial sustainability of small citrus farms by offering a scalable and affordable substitute for current expensive agricultural automation systems. The results show that putting this technology into practice could improve market access for local farmers, lower operating expenses, increase the citrus industry’s resilience in South Africa, restabilizing the market, and reducing poverty in South Africa.

This study examines the effects of consumer confidence, privacy perception and personalized experience on customer satisfaction and repurchase intention in IoT-enabled home technology devices. Smart PLS 4.0 program was used for PLS-SEM method in the study. Although there is generally a positive relationship between perceived ease of use (PEOU) and customer satisfaction in the literature, it is determined that PEOU has no significant effect on customer satisfaction in this study. The effects of data privacy awareness and consumer confidence on customer satisfaction were also not found to be significant. However, data privacy concerns have a positive and significant effect on customer satisfaction, and consumer confidence has a positive and significant effect on repurchase intention. Personalized experiences have positive and significant effects on both customer satisfaction and repurchase intention, and customer satisfaction has a positive and significant effect on repurchase intention.